Pediatric Sydenham's Chorea Information for Patients and Caregivers

Sydenham's chorea is a neurologic movement disorder characterized by irregular, abrupt, relatively rapid involuntary movements (i.e., chorea) of muscles of the face, neck, trunk, and arms and legs (limbs). Additional findings often include diminished muscle tone (hypotonia), muscle weakness, and emotional and behavioral disturbances, particularly obsessive-compulsive behaviors. Sydenham's chorea most frequently occurs in children or adolescents between the ages of 5 to 15 following acute rheumatic fever (ARF). ARF is an inflammatory disease that develops subsequent to throat infection with certain strains of streptococcal bacteria (i.e., group A beta-hemolytic streptococci).

In patients with Sydenham's chorea, choreic movements usually begin gradually, progressively worsening over a few weeks to a month. Associated findings may be extremely variable, ranging from relatively mild incoordination to severe disruption in conducting voluntary movements of multiple muscle groups, potentially affecting speech, arm movements, walking, and the ability to perform certain activities of daily living. In some patients, Sydenham's chorea may a self-limited condition, usually spontaneously resolving within about nine months (average duration) to two years (about 50% of patients); therefore, treatment with certain medications may be restricted to patients with significantly impaired function resulting from severe chorea.

History:
Sydenham's chorea was described in the medical literature in 1686 by Thomas Sydenham, after whom the syndrome is now named. The disorder has also been referred to as...

• St. Vitus' dance
• Acute chorea
• Chorea minor
• Rheumatic chorea

Symptoms/Findings:
Sydenham's chorea is considered a neurological complication following infection with particular strains of streptococci (i.e., group A beta-hemolytic streptococci). The initial illness is usually characterized by a sore throat (pharyngitis) that may be followed, within approximately 1 to 5 weeks, by the sudden (acute) onset of rheumatic fever. The symptom-free period between recovery from pharyngitis to the onset of acute rheumatic fever (ARF) is known as the "latent period." ARF is an inflammatory disease (i.e., sequelae) following group A streptococcal infection that may affect multiple tissues and organs, including the joints, skin, connective tissues directly beneath the skin (subcutaneous tissues), heart, and brain. Associated symptoms and findings may vary greatly from patient to patient. For example, in about 20% of cases, Sydenham's chorea occurs as the only manifestation of ARF; however, in others, it develops as a late feature of ARF following other characteristic manifestations, such as the following:

• Fever, a common initial symptom associated with ARF
• Swelling and inflammation (arthritis) of one or more joints that may be characterized by redness, warmth, tenderness, and pain (arthralgia) of affected joint regions. Arthritis and fever are the most common symptoms initially recognized in association with ARF. Without treatment (e.g., anti-inflammatory drugs), the arthritis progressively affects multiple joints in rapid succession, with the onset of symptoms in different joints typically overlapping. Because arthritic involvement may appear to "migrate" from one joint to the next, this condition is often described as "migratory polyarthritis." Joints of the legs, such as those of the knees and ankles, are typically initially affected, followed by involvement of other areas, including the wrists and elbows. In rare instances, joints of the fingers, toes, or spine may also become involved. Due to extreme tenderness of affected joints, children may experience severe discomfort even due to the presence of clothing, blankets, or bed sheets covering affected joints.
• Inflammation of the heart (carditis). Although often beginning at approximately the same time as fever and arthritis, carditis may not initially cause symptoms (asymptomatic). It is reported that about 80% of patients with Sydenham's chorea have cardiac lesions. The carditis associated with ARF may involve all heart regions (i.e., pancarditis), including...
  
  
  • The internal lining of the heart (endocardium)
  • The relatively thick, middle layer composed of cardiac muscle (myocardium)
  • The fibrous sac (pericardium) surrounding the heart and the roots of its major blood vessels, including the innermost region (i.e., visceral layer) that adheres to the surface of the heart (epicardium)
Carditis may lead to abnormalities in the rate or rhythm of the heart beat (arrhythmias); enlargement of the heart (cardiomegaly) as seen on x-ray imaging; new or changing cardiac murmurs or abnormal heart sounds as heard upon a physician's use of a stethoscope; and, in severe cases, an impaired ability of the heart to pump blood effectively to the lungs and the rest of the body (heart failure). Symptoms of heart failure in affected children may include shortness of breath (dyspnea); nausea and vomiting; a hacking, "nonproductive" cough; and aching or pain within the upper middle (epigastric) or upper right area of the abdomen. In patients with ARF, acute heart inflammation typically gradually subsides within about 5 months. However, in some instances, there may be permanent scarring or damage of certain heart valves, resulting in rheumatic valvular heart disease. In such cases, the mitral valve, located between the left upper and lower heart chambers (left atrium and ventricle), is most commonly affected. As a result, the mitral valve may become abnormally narrow (mitral valve stenosis) and/or may fail to close properly (mitral regurgitation or insufficiency), resulting in a backflow or leakage of blood from the left ventricle into the left atrium during contraction (systole). Less commonly, rheumatic valvular heart disease may also involve other heart valves, such as the valve between the left ventricle and the aorta (aortic valve) and the valve between the right atrium and right ventricle (tricuspid valve).


• "Non-itching" (nonpruritic) skin rash (erythema marginatum) characterized by temporary, pinkish or reddish spots (macules), particularly on the trunk, that gradually fade in the centers. This skin rash tends to appear early in the disease course, may persist or recur when other symptoms have subsided, and usually only affects patients with carditis.
• Subcutaneous nodules or the development of firm, nontender, "pea-sized," node-like structures beneath the skin at various joints, such as the elbows and knees, as well as over the spine. Like erythema marginatum, this relatively infrequent finding typically affects only those with carditis. The subcutaneous nodules tend to appear after the first weeks of the disease course and usually disappear within a week or two.

Choreic movements and emotional or behavioral disturbances
Chorea may also become apparent in patients with ARF, usually developing by 1 to 6 months (or more) following the initial illness (e.g., pharyngitis). However, the average time interval is about eight weeks. As mentioned earlier, Sydenham's chorea may occur as an apparently isolated condition or subsequent to the development of other characteristic features. Although some patients with Sydenham's chorea may have no other symptoms associated with ARF, thorough diagnostic evaluation may reveal cardiac murmurs. (For further information, please see the section entitled "Diagnosis.") In some patients (about 30%), chorea occurs simultaneously with migratory polyarthritis.

In most patients, choreic movements begin acutely, with sudden onset. In some patients, the symptom begin gradually and subtly (insidious), often progressing over weeks to approximately a month before medical attention is sought. In most children, these irregular, involuntary, jerky movements may initially appear as increasing awkwardness or clumsiness, such as difficulty writing. In addition, certain emotional or behavioral abnormalities often develop days or weeks before the onset of chorea, with affected children often described as unusually restless, aggressive, or "excessively emotional."

More specifically, the choreic movements associated with Sydenham's chorea consist of relatively fast or rapid, irregular, uncontrollable, jerky motions that disappear with sleep and may increase with stress, fatigue, excitement, or other factors. When these movements become severe, they develop a ballistic nature. Both sides of the body are typically affected (bilateral). However, in up to 20 percent of patients, abnormal involuntary movements may be unilateral or limited to one side of the body (hemichorea). Affected areas may include muscle groups of the arms and legs (limbs), the trunk, and, in many instances, the face and neck. Many patients also develop muscle weakness.

Associated findings may be variable, ranging from relatively mild incoordination of certain voluntary movements to severe disruption of the ability to perform certain activities of daily living, potentially resulting in significant disability. For example, the neuromuscular abnormalities associated with Sydenham's chorea--including choreic movements, low muscle tone, and/or muscle weakness--may lead to the following:

• Facial grimacing
• A significant deterioration in handwriting (in school-aged children)
• Slight or significant difficulties dressing, feeding, and walking
• Slurred, slowed speech (dysarthria)
• Other associated findings

Rarely, Sydenham's chorea may be associated with decreased muscle tone, muscular rigidity, or increasing muscle stiffness and resistance to movement, resulting in severe disability. In the past, these extremely severe cases (about 1.5% of patients) were said to have "paralytic chorea," as a result of extremely decreased muscle tone. Fortunately, therapies are available to help treat chorea in appropriate, selected cases. (For further information, please see the section entitled "Treatment.")

As mentioned above, Sydenham's chorea is also often associated with emotional or behavioral disturbances. Most commonly, affected children may develop obsessive-compulsive behaviors, which are characterized by the performance of certain repetitive actions or rituals (compulsions) in response to persistent thoughts or impulses (obsessions). In some instances, additional behavioral or emotional abnormalities may also become apparent, including the following:

• Increased irritability
• Frequent mood changes and excessive emotional reactions (emotional lability), including uncontrollable crying episodes
• Age-regressed behaviors
• Confusion
• Easy distractibility, impulsivity, and abnormally increased motor activity (attention deficit hyperactivity)
• Transient psychosis

As mentioned previously, the course of the syndrome may be variable from patient to patient. Associated symptoms may tend to begin relatively subtly, progressively worsen over a few weeks to months (usually over 2 to 4 weeks), and gradually spontaneously resolve within approximately 3 to 6 months. However, in some instances, there may be residual signs of chorea and behavioral abnormalities, which may wax and wane over a year or more. In addition, in about 20 percent of patients, Sydenham's chorea may recur, usually within approximately 2 years of the initial occurrence. Recurrences have also been reported during pregnancy in women who had ARF during childhood as well as in association with the administration of certain medications (e.g., estrogen-containing oral contraceptives; phenytoin, an anticonvulsant agent).

Age at Onset/Epidemiology:
Acute rheumatic fever (ARF) is relatively rare in the United States, occurring much less commonly than seen in developing countries. The frequency of ARF dramatically declined in the U.S. and Western Europe during the 1960s and 1970s. The lower incidence of the disease in developed countries has been attributed to routine, early use of antibiotic therapy to treat streptococcal infections. However, for unknown reasons, the frequency of ARF has recently been increasing in the U.S. For example, outbreaks were recorded in the 1990s in Pennsylvania and in the 1980s in Ohio and Utah resulting from infection with a strain of group A streptococci that had previously been rare in the U.S. In addition, at least 2 outbreaks occurred in military recruit populations in the U.S. from the mid- to the late 1980s. Although the reasons for this apparent resurgence are unknown, researchers indicate that more virulent streptococcal strains may be returning to the U.S. In underdeveloped areas, ARF remains a major health problem. For instances, 50% of all heart surgeries in Brazil are performed to correct rheumatic cardiac lesions.

In the past, reports suggested that Sydenham's chorea occurred in up to 50 percent of patients with acute rheumatic fever. However, more recent evidence indicates that the condition develops in 26% of ARF patients.

Sydenham's chorea affects females approximately twice as frequently as males, particularly in the years around puberty. As a result, some researchers suggest that sex hormones (e.g., the female hormone estrogen) may play some role in the development of the syndrome. (For further information, see the section entitled "Causes/Pathophysiology.") Sydenham's chorea most frequently occurs in children or adolescents between the ages of 5 to 15. However, as mentioned previously, about 20 percent of patients may have a second occurrence, particularly within 2 years following the initial episode. In addition, recurrences have been reported during pregnancy in women who had ARF during childhood and in patients in association with the administration of certain therapies, including estrogen-containing oral contraceptives and the anticonvulsant medication phenytoin.

Causes/Pathophysiology:
Acute rheumatic fever (ARF) is a delayed inflammatory reaction in response to a streptococcal bacterial infection (i.e., with group A beta-hemolytic streptococci). Members of certain families appear to have an increased risk of ARF and rheumatic heart disease. In addition to possible hereditary factors, certain environmental factors, including overcrowded living conditions and malnutrition, are also thought to play some role in increasing susceptibility to streptococcal infections as well as the risk of subsequent ARF. Also, as mentioned previously, some investigators suggest that sex hormones (e.g., the female hormone estrogen) may be a contributing factor in some instances of Sydenham's chorea. This is based upon various findings, including the fact that females are more commonly affected than males, particularly in the years around puberty, and that recurrences have been associated with estrogen therapy or pregnancy.

The specific underlying mechanism(s) responsible for development of ARF remain unknown. However, evidence suggests that the disorder may result from an abnormal immune reaction in which antibodies produced in response to the invading bacterium act against certain of the body's own cells. For example, according to such a theory (sometimes known as "autoimmune mimicry"), a foreign protein (antigen) from a particular bacterium may be similar to one of the body's own proteins; as a result, the human immune system may be unable to distinguish between its "self" protein and that of the invading microorganism, potentially triggering an inappropriate autoimmune response. The symptom-free period between recovery from sore throat (pharyngitis) to the onset of symptoms associated with ARF (i.e., latent period) may lend support to the theory of an abnormal immune mechanism resulting in tissue damage.

In addition, experts suggest that Sydenham's chorea appears to result from such an autoimmune response. Evidence indicates that certain streptococcal proteins or antigens (streptococcal M proteins) induce the body's production of antibodies (i.e., antineuronal antibodies) that "crossreact" against the body's own cells in certain regions of the brain. (Group A streptococcal M protein has been shown to contain some of the same amino acid sequences as within certain human tissues.) Furthermore, some researchers have reported detecting certain antibodies (e.g., immunoglobulin G [IgG] antibodies) in children with Sydenham's chorea that interacted with certain cellular proteins (i.e., neuronal antigens) in the basal ganglia, such as the caudate nuclei and subthalamic nucleus. The basal ganglia are paired nerve cell clusters deep within the brain that play an essential role in initiating and regulating movement.

In another study, researchers determined that, during acute attacks, 80 percent of patients with ARF had antibodies against cardiolipin (anticardiolipin antibodies). Cardiolipin is a fatty compound (i.e., phospholipid) located within human mitochondrial inner membranes and bacterial cellular membranes. There was not a significant difference in the percentage of patients with antibodies who did or did not have Sydenham's chorea.

As mentioned above, Sydenham's chorea appears to result from an autoimmune or antibody-mediated inflammatory response involving certain regions of the basal ganglia. Experts indicate that the results of certain neuroimaging studies may provide further information concerning underlying disease processes (i.e., pathophysiology) involved in Sydenham's chorea. For example, such studies have demonstrated abnormally increased metabolism (hypermetabolism) in certain regions of the brain, findings that may reflect the autoimmune process. More specifically, positron emission tomography (PET) scanning has shown increased glucose metabolism within major substructures of the basal ganglia (i.e., striatum), a finding that was reversed with clinical improvement. This is in marked contrast to Huntington's disease (HD) and other hereditary forms of chorea, in which PET demonstrates decreased glucose and oxygen metabolism. In addition, magnetic resonance imaging (MRI) of patients with Sydenham's chorea has shown abnormally increased size of the 3 major substructures that form the basal ganglia, including the caudate nuclei, the globus pallidus, and the putamen, possibly providing evidence of an inflammatory process.

Diagnosis:
A diagnosis of Sydenham's chorea is primarily based upon a thorough clinical evaluation, detection of characteristic symptoms and findings, and a careful patient history. Because the initial illness (e.g., pharyngitis) may precede the onset of chorea by as much as 6 months or more, many patients (or their parents) may not provide a history of streptococcal infection. In addition, there may be minimal or no evidence of recent infection with group A streptococci. Evidence of recent streptococcal infection may include...

• Elevated levels of certain antibodies to streptococci (e.g., antistreptolysin O [ASO] or other antistreptococcal antibodies) in the blood. Although up to 80 percent of patients with ARF have elevated levels of ASO, many individuals with Sydenham's chorea may have negative results with such testing.
• A positive throat culture. A throat culture involves swabbing the back of the throat with a sterile applicator to obtain material for laboratory analysis that may help to identify certain bacteria, including group A beta-hemolytic streptococci. Throat cultures are often negative by the time of symptom onset in those with ARF. Conversely, up to 60% to 80% of healthy teenagers may have an asymptomatic positive throat culture. Therefore, the specificity and sensitivity of this test is very low.
• Elevated erythrocyte sedimentation rate (ESR). ESR, also known as the "sed rate," is a laboratory test that measures the rate at which red blood cells (erythrocytes) settle to the bottom of a specialized test tube, leaving the fluid portion of the blood at the top of the tube. This test serves as a nonspecific indicator of inflammation, since red blood cells tend to clump together and settle more quickly to the bottom of the blood sample when inflammation is present. ESR may also be used to help adjust dosage levels of anti-inflammatory drugs during treatment of patients with certain inflammatory diseases. Although the ESR may remain elevated in those with ARF for months, the results may be normal in some patients who initially receive medical attention due to the sole or late manifestation of Sydenham's chorea.

As mentioned earlier, chorea may or may not occur in association with other symptoms and findings associated with acute rheumatic fever (ARF). In addition, there is no single clinical feature or laboratory test that definitively establishes a diagnosis of ARF. Instead, the presence of certain clinical findings, termed "Jones criteria," suggests a probable diagnosis of ARF. The most current, revised Jones criteria for the diagnosis of ARF (revised in 1992 by the American Heart Association) include confirmation of 2 major criteria or 1 major and 2 minor criteria, in addition to evidence of recent streptococcal group A infection. Major criteria include migratory polyarthritis, carditis, erythema marginatum, subcutaneous nodules, and chorea. (For further information, please see the section entitled "Symptoms/Findings.") Minor criteria include less specific findings, such as fever; joint discomfort (arthralgia) in the absence of redness, warmth, or pain upon physical examination; and certain findings detected by diagnostic tests. These include...

• An elevated ESR (see above)
• Elevated levels of C-reactive protein (CRP) in the blood. Levels of CRP rise in response to inflammation, thus serving as a nonspecific indicator of an inflammatory process. As with ESR, CRP levels may be used to help adjust dosage levels of anti-inflammatory drugs used to help treat certain inflammatory diseases.
• Prolonged P-R interval on an electrocardiogram (ECG), which is a diagnostic test that records electrical activity of heart muscle (myocardium). This is a nonspecific finding in which an ECG records a slightly increased delay between contractions of the upper and lower chambers of the heart.

Experts indicate that some patients may be diagnosed with acute rheumatic fever in the absence of the criteria described above. Such exceptions to the Jones criteria include those patients with...

• Chorea (i.e., Sydenham's chorea), if other possible causes of choreic movements have been excluded
• Late-onset or insidious carditis with no other likely cause

In addition, a recurrence of ARF should be considered in those with prior rheumatic fever or rheumatic valvular heart disease and evidence of a recent preceding streptococcal infection with 1 major or 2 minor criteria.

Thus, again, a diagnosis of Sydenham's chorea is generally based upon characteristic symptoms and findings and a complete patient history, revealing a relatively recent onset of symptoms. Diagnostic evaluation may include clinical assessments to detect certain signs potentially associated with chorea, such as an inability to maintain protrusion of the tongue or a finding known as "relapsing grip" (or "milking sign"). To detect the latter, the physician asks the patient to squeeze his or her (i.e., the examiner's) hand; in those with Sydenham's chorea, the patient's grip may continuously, erratically increase and decrease.

For some patients, neurologic assessment may include certain neuroimaging studies, such as magnetic resonance imaging (MRI). In those with Sydenham's chorea, EEG results are frequently abnormal, with irregular slowing of certain brain wave patterns. Also, as mentioned previously, MRI may reveal increased size of certain regions of the basal ganglia or other findings.

Once a diagnosis of Sydenham's chorea is considered, a thorough cardiac evaluation should also be conducted to rule out or confirm possible cardiac involvement. Such assessment includes evaluation of heart and lung sounds through use of a stethoscope to detect new or changing cardiac murmurs that may result from altered blood flow through certain heart valves. X-ray imaging may reveal enlargement of the heart (cardiomegaly), a finding commonly seen in those with significant carditis. In addition, more sensitive techniques may be conducted to record the heart's electrical activity (electrocardiography) and to create an image of the structure of the heart through the use of reflected sound waves (echocardiography), thereby assisting physicians in detecting and characterizing structural or functional abnormalities of the heart.

The differential diagnosis of Sydenham's chorea includes chorea associated with systemic lupus erythematosus (SLE) or other post-infectious choreas (particularly in relationship with viral infections). Other considerations include familial forms of chorea, exposure to particular toxins, the use of certain medications, central nervous system lesions, or other conditions that may be associated with similar symptoms or findings.

Treatment:
Adequate antibiotic therapy for children with streptococcal infections may help to prevent the onset of an initial attack of acute rheumatic fever (ARF). More specifically, such preventive therapy (i.e., primary prophylaxis) introduced up to about a week after the onset of streptococcal sore throat (pharyngitis) can prevent the onset of ARF.

The management of children with ARF may include restriction of normal activities and prompt administration of penicillin by mouth (orally) or intramuscular injection or other appropriate antibiotic therapies. Experts indicate that antibiotic therapy should be provided for all patients with ARF at the time of diagnosis since it may initially be difficult to confirm recent streptococcal infection due to the latent period, particularly in those with Sydenham's chorea. In addition, depending upon the severity of joint inflammation (arthritis) and heart inflammation (carditis), treatment may be provided with certain medications to help reduce pain and/or inflammation. For example, for those with arthritis, therapy may include codeine or salicylates, such as aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). (As mentioned previously, early administration of salicylate therapy before diagnostic confirmation may confuse the diagnosis by preventing development of classic migratory polyarthritis. Thus, until the disease's clinical course has become evident, with subsequent diagnostic confirmation, experts recommend avoiding early therapy with anti-inflammatory agents and instead providing codeine or other similar agents for those with painful arthritis. On a cautionary note, the administration of aspirin or salicyliate in children may cause the rare but often fatal Reye syndrome.)

For patients with heart failure and other significant symptoms of carditis, therapy requires the administration of corticosteroid agents, such as prednisone. However, patients with mild carditis without signs of heart failure may receive sufficient benefit from salicylate therapy alone.

For those who receive salicylate therapy, blood levels and liver function must be regularly monitored (i.e., with blood and urine tests) to help reduce the possibility of salicylate toxicity, a condition that may be characterized by headache, rapid breathing (tachypnea), vomiting, irritability, reduced levels of sugar in the blood (hypoglycemia), and/or other findings. Steroid therapy should be limited in duration and dosage levels to help reduce adverse effects. In addition, such therapy should not be abruptly discontinued; rather, dosage levels should be gradually reduced (tapered down). As steroid dosage levels are tapered, physicians may recommend adding salicylates to help prevent a possible "rebound" of inflammatory symptoms. Salicylate therapy may be continued for approximately 2 to 4 weeks following the cessation of steroid administration.

For patients with heart failure, treatment may include the use of additional medications, such as diuretics to help eliminate excess fluid; certain heart medications that may strengthen contractions of the heart (cardiac glycosides, e.g., digitalis); and continued bed rest as required (although prolonged bed rest is typically unnecessary). Rarely, if such therapy is not effective, certain surgical measures may be required to replace or surgically repair damaged heart valves or to widen (dilate) narrowed valves through use of a balloon-tipped catheter (valvuloplasty).

As Sydenham's chorea may spontaneously resolve or not cause significant functional impairment, many experts indicate that treatment with certain medications, such as dopamine blockers (antagonists), should be avoided unless associated chorea is functionally disabling or associated with potentially violent flailing motions of the limbs that may result in self-injury. Dopamine antagonists, such as the antipsychotic agents haloperidol (Haldol®) or pimozide (Orap®), may have potentially severe adverse effects, including the development of tardive dyskinesia. First-line therapy with the anticonvulsant medication valproate sodium (Depakene®) may be beneficial for some patients with Sydenham's chorea. Pimozide is usually reserved for those patients who fail to respond to valproate or who present with severe forms (i.e., chorea paralytica). If these two options fail, the next steps may include immunomodulatory treatment, steroids, IV IgG, or plasmapheresis.

Experts indicate that patients who have had ARF or Sydenham's chorea should receive ongoing therapy to help prevent recurrences of rheumatic fever. Such preventive (i.e., secondary prophylactic) therapy may include intramuscular penicillin injections (benzathine penicillin G) every 21 days, daily penicillin by mouth (orally), or oral daily therapy with the antibacterial medication sulfadiazine or the antibiotic erythromycin (if other medications cannot be taken). Some experts indicate that prophylactic therapy should be lifelong for all those affected by ARF or chorea. Others recommend that therapy should be provided after an acute attack for 5 years or up to age 18 (whichever comes first) and should be longer only for those who have significant rheumatic valvular heart disease or an increased risk of reinfection (e.g., those who live in crowded conditions, health care professionals, teachers, etc.). Still others indicate that such secondary prophylaxis should be lifelong for all those with rheumatic heart disease. Individuals with rheumatic valvular disease are at an increased risk for developing bacterial infection of the heart valves and the lining of the heart chambers (endocarditis).

Additional Resources

Advocacy/Support Organizations

NIH/National Institute of Neurological Disorders and Stroke (NINDS)
9000 Rockville Pike
Bethesda, MD 20892
Phone: (301) 496-5751
Toll-free: (800) 352-9424
Web site: http://www.ninds.nih.gov/

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